Abstract
BackgroundApplication of cardiac stem cells combined with biomaterial scaffold is a promising therapeutic strategy for heart repair after myocardial infarction. However, the optimal cell types and biomaterials remain elusive.MethodsIn this study, we seeded Isl1+ embryonic cardiac progenitor cells (CPCs) into decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) to assess the therapeutic potential of Isl1+ CPCs and the biocompatibility of SIS-ECM with these cells.ResultsWe observed that SIS-ECM supported the viability and attachment of Isl1+ CPCs. Importantly, Isl1+ CPCs differentiated into cardiomyocytes and endothelial cells 7 days after seeding into SIS-ECM. In addition, SIS-ECM with CPC-derived cardiomyocytes showed spontaneous contraction and responded to β-adrenergic stimulation. Next, patches of SIS-ECM seeded with CPCs for 7 days were transplanted onto the outer surface of infarcted myocardium in mice. Four weeks after transplantation, the patches were tightly attached to the surface of the host myocardium and remained viable. Transplantation of patches improved cardiac function, decreased the left ventricular myocardial scarring area, and reduced fibrosis and heart failure.ConclusionsTransplantation of Isl1+ CPCs seeded in SIS-ECM represents an effective approach for cell-based heart therapy.
Highlights
Application of cardiac stem cells combined with biomaterial scaffold is a promising therapeutic strategy for heart repair after myocardial infarction
In order to investigate whether the patches supported cell survival, viable Isl1+ Cardiac progenitor cell (CPC) prestained with Dil (Invitrogen) were observed by bright-field and fluorescence microscopy (Fig. 1e, f) at 24 hours after seeding
DAPI staining of frozen sections showed that Isl1+ CPCs remained viable in small intestinal submucosa extracellular matrix (SIS-ECM) patches (Fig. 1g, h)
Summary
Application of cardiac stem cells combined with biomaterial scaffold is a promising therapeutic strategy for heart repair after myocardial infarction. Results: We observed that SIS-ECM supported the viability and attachment of Isl1+ CPCs. Importantly, Isl1+ CPCs differentiated into cardiomyocytes and endothelial cells 7 days after seeding into SIS-ECM. Patches of SIS-ECM seeded with CPCs for 7 days were transplanted onto the outer surface of infarcted myocardium in mice. Transplantation of patches improved cardiac function, decreased the left ventricular myocardial scarring area, and reduced fibrosis and heart failure. Conclusions: Transplantation of Isl1+ CPCs seeded in SIS-ECM represents an effective approach for cell-based heart therapy. Previous studies have confirmed that ischemic cardiomyocyte death, myocardial fibrosis, and inflammation are characteristic pathological features of cardiac remodeling after MI [2, 3]. Various types of cells have been combined with different materials for cardiac repair and generation of new myocardium, including induced
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